Effects of some ergot derivatives in bone marrow of mice

The in vivo chromosomal damaging properties of some ergot derivatives were investigated following their administration to male mice. Dihydroergotoxine, ergotamine and methysergide were injected in doses of 25, 50 and 100 mg/kg. Significant numbers of aberrations were observed in bone marrow preparations after treatment with the higher doses. Almost all the damage was in the form of chromatid aberrations. No exchange figures were observed, neither were other anamalies, such as nondisjunction or anti-mitotic activity. This frequency of damage was about 7- to 10-fold less than that produced by the powerful alkylating agent, cyclophosphamide. Thus the ergot derivatives were concluded to have weak chromosomal damaging effects in vivo only in very high doses.     

Effects of different levels of ergot in concentrates on the growing and slaughtering performance of bulls and on carry-over into edible tissue

The aim of the present study was to examine long-term effects of low levels of ergot alkaloids on growing bulls. Natural grown ergot with a mean total alkaloid concentrations of 633 mg/kg, and ergotamine (25%), ergocristine (15%) and ergosine (13%) as the most prominent alkaloids, was used. In a dose-response study 38 Holstein Friesian bulls were fed with three different doses of this ergot (0, 0.45 and 2.25 g/kg concentrate corresponding to an average total alkaloid concentration of the daily ration of 0, 69 and 421 microg/kg DM) over a period of approximately 230 days. Live weight, feed intake and health condition were monitored over the entire test period. The bulls were slaughtered at a live weight of approximately 550 kg. Carcass composition and quality were recorded and samples of liver, muscle, kidneys, fat, bile, urine and blood were analysed for ergot alkaloids. Liver enzyme activities and total bilirubin were measured in the blood. Statistically, no significant differences were detectable between the three feeding groups. Mean live weight gain over all groups was 1.41 kg/d with a mean dry matter intake of 7.35 kg/d. No carry over into tissues could be proved out of the experiment. To derive a no-effect level for beef cattle further research including higher ergot doses will be necessary.     

Effects of different levels of ergot in concentrates on the growing and slaughtering performance of bulls and on carry-over into edible tissue

Abstract

The aim of the present study was to examine long-term effects of low levels of ergot alkaloids on growing bulls. Natural grown ergot with a mean total alkaloid concentrations of 633 mg/kg, and ergotamine (25%), ergocristine (15%) and ergosine (13%) as the most prominent alkaloids, was used. In a dose-response study 38 Holstein Friesian bulls were fed with three different doses of this ergot (0, 0.45 and 2.25 g/kg concentrate corresponding to an average total alkaloid concentration of the daily ration of 0, 69 and 421 µg/kg DM) over a period of approximately 230 days. Live weight, feed intake and health condition were monitored over the entire test period. The bulls were slaughtered at a live weight of approximately 550 kg. Carcass composition and quality were recorded and samples of liver, muscle, kidneys, fat, bile, urine and blood were analysed for ergot alkaloids. Liver enzyme activities and total bilirubin were measured in the blood. Statistically, no significant differences were detectable between the three feeding groups. Mean live weight gain over all groups was 1.41 kg/d with a mean dry matter intake of 7.35 kg/d. No carry over into tissues could be proved out of the experiment. To derive a no-effect level for beef cattle further research including higher ergot doses will be necessary.     

Influence of centrally administered somatostatin and two related peptides on intestinal absorption of water and electrolytes in conscious dogs

The effects of intracerebroventricular (ICV) administration of somatostatin (SRIF) and two related peptides, anti SRIF and SMS 201-995, on jejunal fluxes of water, Na+ and K+ were investigated in dogs prepared with a Thiry-Vella (TV) loop. Intestinal transport in the TV loop and concomitant transit time were also measured during infusion (2 mg/min) of an isotonic electrolyte solution and phenol-red bolus injections. Basal net water absorption was reduced significantly (p less than 0.01) over periods of 2 to 5 hr and in a dose-related manner, with ICV administrations of SRIF (5 to 100 ng/kg); doses of SRIF, 5 to 25 times higher but administered IV, were inactive. Similar reductions in the net fluxes of water, Na+ and K+ were observed over 2 to 5 hr following ICV administration of a putative somatostatin antagonist and SMS 201-995 at doses of 100 ng/kg. Neither metoclopramide (1 mg/kg), phentolamine (0.1 mg/kg) nor methysergide (0.2 mg/kg) given IV were able to antagonize the effects of centrally administered SRIF (100 ng/kg) on intestinal fluxes. In contrast, the effects of SRIF were abolished completely by naloxone (0.2 mg/kg) but not methyl-naloxone (0.3 mg/kg) given systemically. It is concluded that somatostatin and the two related peptides act centrally to reduce jejunal absorption of water and electrolytes. The effects of SRIF appear to be related to opiate receptors, possible involving central nerve pathways which utilize opiate-like transmitters.     

Comparative studies on the effect of ergot contaminated feed on performance and health of piglets and chickens

Two dose response trials were conducted with piglets and chickens to study the effects of increasing amounts of ergot (Claviceps purpurea) with a defined alkaloid content and pattern on performance, biochemical serum characteristics and organ weights (of chickens). The ergot was mixed into the cereal-soybean meal based diets at levels of 0, 0.5, 1, 2 and 4?g/kg. The total alkaloid content of the ergot was analysed to be 2775?mg/kg and showed the following composition: ergometrine 8.1%, ergotamine 5.4%, ergocornine 3.2%, α-ergocryptine 1.9%, ergocristine 14.9% and residue 66.5%. Each treatment was tested with eight castrated male and eight female piglets over a period of 35 days (8?kg initial live weight) and 28 male chickens for 21 days (43?g initial live weight). Cumulative daily dry matter intake and live weight gain [g/d] were 595, 535, 560, 577 and 490 and 413, 399, 420, 443 and 347 for the piglets fed the unsupplemented control diet and the diets containing 0.5, 1, 2 and 4?g ergot per kg, respectively. Feed intake and live weight gain of the piglets fed the highest ergot supplemented diet were significantly decreased. Serum aspartate aminotransferase activity of the 4?g ergot treatment was significantly increased. Also serum albumin concentrations showed significant linear alterations. Serum activities of glutamate dehydrogenase, γ-glutamyltransferase, total protein and porcine growth hormone were not significantly influenced by dietary treatment. The experiment with chickens demonstrated no significant effects on performance due to dietary ergot exposure. The serum activities of glutamate dehydrogenase and alanine aminotransferase were not significantly influenced by dietary treatment while serum activities of γ-glutamyltransferase and aspartate aminotransferase and the concentrations of albumin and total bilirubin were significantly affected. Heart weights showed a significant linear decrease due to ergot feeding. According to these results, piglets seemed to react more sensitively on the occurrence of ergot in the diet as compared to chickens. The critical level of total ergot alkaloids for piglets seemed to be in the range from 5.6?mg to 11.1?mg/kg diet for the present study. Ergot effects on signs of inflammation in the proximal duodenum occurred in chickens fed diets containing 2.8?mg and 11.1?mg total ergot alkaloids/kg although live performance remained unaffected. Further studies are necessary to define the critical level of ergot alkaloids in dependence on alkaloid pattern.     

Dihydroergotoxine decreases blood pressure in spontaneously hypertensive rats by interacting with peripheral dopamine receptors

Dihydroergotoxine (10 micrograms/kg s.c.) decreased mean carotid blood pressure in urethane-anaesthetized spontaneously hypertensive rats but failed to modify the same parameter in normotensive rats. The effect was statistically significant 20 min after the injection and relatively long lasting (up to 90 min). Pharmacological characterization of the phenomenon indicated that it is mediated by stimulation of dopamine receptors, since pretreatment with haloperidol, cis-flupentixol but not with trans-flupentixol, completely prevent the reduction in blood pressure induced by dihydroergotoxine. Moreover, a challenge dose of dihydroergotoxine did not reduce mean blood pressure values in spontaneously hypertensive rats pretreated with domperidone or (-)sulpiride, but not with (+)sulpiride. These results suggest that the ergot derivative modifies the cardiovascular system by interaction with peripheral dopamine receptors of the DA2 type.     

Comparative studies on the effect of ergot contaminated feed on performance and health of piglets and chickens

Two dose response trials were conducted with piglets and chickens to study the effects of increasing amounts of ergot (Claviceps purpurea) with a defined alkaloid content and pattern on performance, biochemical serum characteristics and organ weights (of chickens). The ergot was mixed into the cereal-soybean meal based diets at levels of 0, 0.5, 1, 2 and 4 g/kg. The total alkaloid content of the ergot was analysed to be 2775 mg/kg and showed the following composition: ergometrine 8.1%, ergotamine 5.4%, ergocomine 3.2%, alpha-ergocryptine 1.9%, ergocristine 14.9% and residue 66.5%. Each treatment was tested with eight castrated male and eight female piglets over a period of 35 days (8 kg initial live weight) and 28 male chickens for 21 days (43 g initial live weight). Cumulative daily dry matter intake and live weight gain [g/d] were 595, 535, 560, 577 and 490 and 413, 399, 420, 443 and 347 for the piglets fed the unsupplemented control diet and the diets containing 0.5, 1, 2 and 4 g ergot per kg, respectively. Feed intake and live weight gain of the piglets fed the highest ergot supplemented diet were significantly decreased. Serum aspartate aminotransferase activity of the 4 g ergot treatment was significantly increased. Also serum albumin concentrations showed significant linear alterations. Serum activities of glutamate dehydrogenase, gamma-glutamyltransferase, total protein and porcine growth hormone were not significantly influenced by dietary treatment. The experiment with chickens demonstrated no significant effects on performance due to dietary ergot exposure. The serum activities of glutamate dehydrogenase and alanine aminotransferase were not significantly influenced by dietary treatment while serum activities of gamma-glutamyltransferase and aspartate aminotransferase and the concentrations of albumin and total bilirubin were significantly affected. Heart weights showed a significant linear decrease due to ergot feeding. According to these results, piglets seemed to react more sensitively on the occurrence of ergot in the diet as compared to chickens. The critical level of total ergot alkaloids for piglets seemed to be in the range from 5.6 mg to 11.1 mg/kg diet for the present study. Ergot effects on signs of inflammation in the proximal duodenum occurred in chickens fed diets containing 2.8 mg and 11.1 mg total ergot alkaloids/kg although live performance remained unaffected. Further studies are necessary to define the critical level of ergot alkaloids in dependence on alkaloid pattern.     

Effect of various antagonists on the Channa striatus fillet extract antinociception in mice

The effects of an aqueous supernatant of haruan (ASH) (Channa striatus) fillet extract on various antinociception receptor system activities were examined using a mouse abdominal-constriction model. Mice that were pretreated with distilled water, s.c., followed 10 min later by administration of 25%, 50%, and 100% concentration ASH, s.c., produced a significant concentration-dependent antinociceptive activity (p < 0.001). Pretreatment with naloxone (0.3, 1.0, and 3.0 mg/kg body mass), 10 min before ASH administration, failed to block the extract antinociception. Pretreatment of the 100% concentration ASH with mecamylamine (5 mg/kg), pindolol (10 mg/kg), and haloperidol (1 mg/kg) also did not cause any significant change in its antinociception. However, pretreatment with atropine (5 mg/kg), bicuculline (10 mg/kg), phenoxybenzamine (10 mg/kg), and methysergide (5 mg/kg) were found to reverse ASH antinociception. Based on the above findings, the ASH is suggested to contain different types of bioactive compounds that act synergistically on muscarinic, GABAA, alpha-adrenergic, and serotonergic receptor systems to produce the observed antinociception.     

In vivo mutagenicity studies with iodinated glycerol azeo

Previous studies have shown that iodinated glycerol azeo is positive in a number of in vitro mutagenicity assays including the Ames assay (TA100; TA1535), mouse lymphoma assay, Chinese hamster ovary (cytogenetic) assay and in one in vivo study, the sex-linked-recessive-lethal assay in Drosophila. Prior studies have also shown that the drug is negative in the mouse micronucleus assay. We now report that the drug is also negative for mutagenic activity in a number of other in vivo tests. Single intraperitoneal doses of 25, 125 and 250 mg/kg were without effect in the rat bone marrow chromosomal aberration assay. Single oral doses of 30, 75, 150 and 300 were negative in the rat hepatocyte DNA-repair assay. Single intraperitoneal doses of 30 and 100 mg/kg were without effect in the sister chromatid exchange (SCE) assay in the mouse. Statistically significant effects were seen at 200 and 300 mg/kg in the initial SCE assay and at 300 and 350 mg/kg in the confirmatory SCE assay. The rationale for considering the SCE results to be anomalous and thus not relative to the overall safety evaluation of the drug is presented.     

Effect of ergot alkaloids on 3H-flunitrazepam binding to mouse brain GABAA receptors

In vitro effects of dihydroergotoxine, dihydroergosine, dihydroergotamine, alpha-dihydroergocriptine (ergot alkaloids), diazepam, methyl-beta-Carboline-3-carboxilate (beta-CCM), flumazenil (benzodiazepines), gamma-amino butyric acid (GABA) and thiopental (barbiturate) were studied on mouse brain (cerebrum minus cerebral cortex) benzodiazepine binding sites labeled with 3H-flunitrazepam. Specific, high affinity (affinity constant, Kd = 57.7 8.6 nM) binding sites for 3H-flunitrazepam on mouse brain membranes were identified. All benzodiazepine drugs inhibited 3H-flunitrazepam binding with nanomolar potencies. In contrast to benzodiazepines, all ergot drugs, GABA and thiopental produced an enhancement of 3H-flunitrazepam binding to its binding site at the GABAA receptor of the mouse brain. The rank order of potency was: neurotransmitter (GABA) > dihydroergotoxine > thiopental > alpha-dihydroergocriptine > dihydroergosine > dihydroergotamine. The results suggest that dihydrogenated ergot derivatives do not bind to the brain benzodiazepine binding sites labeled with 3H-flunitrazepam. However, an enhancement of 3H-flunitrazepam binding by all ergot drugs tested, clearly identifies an allosteric interaction with the benzodiazepine binding sites of GABAA receptors.     

Filaricidal efficacy of anthelmintically active cyclodepsipeptides

PF 1022A, a novel anthelmintically active cyclodepsipeptide, and Bay 44-4400, a semisynthetic derivative of PF 1022A were tested for filaricidal efficacy in Mastomys coucha infected with Litomosoides sigmodontis, Acanthocheilonema viteae and Brugia malayi. The parent compound PF 1022A showed limited anti-filarial efficacy in L. sigmodontis and B. malayi infected animals. Oral doses of 5 x 100 mg/kg on consecutive days caused only a temporary decrease of microfilariaemia levels. By contrast, Bay 44-4400 was highly effective against microfilariae of all three species in single oral, subcutaneous and cutaneously applied (spot on) doses. Minimum effective doses (MED, reducing parasitaemia density by > or =95%) determined 3 and 7 days after treatment were 3.125-6.25 and 6.25-12.5mg/kg, respectively. Using the spot on formulation, doses of 6.25mg/kg (L. sigmodontis), 12.5mg/kg (A. viteae) and 25mg/kg (B. malayi) were required to cause reductions of microfilaraemia levels by > or =95% until day 56. Adulticidal effects, determined as minimum curative doses (MCD, eliminating adult parasites within 56 days by >95%) after single dose treatment were limited to A. viteae (MCD, 100mg/kg independent of the route of administration). Repeated oral treatment (100mg/kg on 5 consecutive days) killed all adult L. sigmodontis but did not affect B. malayi. However, single doses of 6.25 and 25mg/kg resulted in severe pathological alterations of intrauterine stages of L. sigmodontis and B. malayi, respectively. These alterations may be responsible for long-lasting reductions of microfilaraemia even when curative effects could not be achieved.     

Effects of different levels of ergot in concentrate on the health and performance of male calves

A number of studies dealing with the effects of ergot and ergot alkaloids on the health and performance of poultry and pigs were reported in the past, but only a few studies and field reports are available for ruminants. Therefore, a dose-response study was carried out with calves since young animals are considered to be especially sensitive to ergot. A total of 35 male Holstein calves were randomly assigned to three feeding groups after one month of feeding milk replacer. The mean initial live weight of the calves was 49.4±5.7 kg. One control group was fed an ergot-free concentrate (n=12), one group an ergot proportion of 1000 mg/kg in the concentrate (n=ll), and another group was fed a concentrate containing 5000 mg/kg ergot (n=12). Hay, grass silage and water were available forad libitum consumption, whereas the daily concentrate portion was restricted to 2 kg. Live weight, health parameters and feed intake were monitored over the experimental period of 84 days. In addition, blood samples were taken from theVena jugularis at the beginning and at the end of the experiment and analysed for ergot alkaloids and liver parameters. Total dry matter intake, live weight gain and feed-to-gain ratio were not significantly influenced by increasing ergot proportions when the whole experimental period was considered, although there was a trend for an ergot-related decrease in concentrate intake during the first 6 weeks of the experiment. After this period of time, it seemed that calves got used to the presence of ergot in the concentrate and were able to adjust their intake to the level of the control group. Moreover, health and liver parameters, such as total bilirubin, aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transpeptidase and creatine kinase in the serum were not significantly influenced by dietary treatments. Concentrations of the individual ergot alkaloids in serum were lower than the detection limits of the applied HPLC-method. In conclusion, it can be assumed that an ergot contamination of the concentrate up to 5000 mg/kg resulted in a transient depression of concentrate intake by the calves. However, no significant effects on health and performance could be detected when the entire test period of 84 days was considered. Presented at the 28^th Mykotoxin-Workshop, Bydgoszcz, Poland, May 29–31, 2006     

Effect of 2-deoxy-D-glucose on gonadotropins,prolactin and serum glucose concentrations in the mare

In a variety of species, glucoprivation results in the suppression of the reproductive axis. Two experiments were performed to test the hypothesis that blockade of glucose metabolism via administration of the glucose inhibitor 2-deoxy-D-glucose (2DG) to mares would cause a modification in gonadotropin and prolactin secretion. Long-term ovariectomized mares (Experiment 1, n=4) or ovary-intact mares during the follicular phase of a synchronized estrous cycle (Experiment 2, n=4 per dose) were treated with 2DG. The dose of 2DG used in Experiment 1 was 100mg 2DG/kg BW, but because severe behavioral responses occurred, lower doses (50, 25, and 12.5mg 2DG/kg BW) were used for Experiment 2. In addition to the effects of 2DG, the pituitary responsiveness after glucoprivation was determined by an injection of gonadotropin-releasing hormone (100 microg) 6h post-treatment. In both experiments, treatment with 2DG was unaccompanied by changes in gonadotropin secretion or pituitary responsiveness. Mares treated with 100 mg 2DG/kg BW exhibited a significant increase in prolactin and mares treated with 100mg 2DG or 50mg 2DG/kg BW exhibited a significant increase in serum glucose concentrations, suggesting that glucoprivation was detected at these doses. Lower doses of 2DG did not cause significant alterations in prolactin or glucose levels. These results indicate that 2DG inhibits glucose utilization, but short-term glucoprivation via this metabolic inhibitor does not alter gonadotropin secretion in the mare. This lack of response to glucoprivation may reflect species differences in the response to glucoprivation or may be due to metabolic responses to the inhibition of glucose availability.     

Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats

The effects of oral administration of aqueous extract of Bulbine natalensis Baker stem at daily doses of 25, 50, and 100 mg/kg body weight on the reproductive function of Wistar rats were evaluated. The indices of mating and fertility success as well as quantal frequency increased after 7 days of treatment in all the dose groups except the 100 mg/kg body weight group. The number of litters was not statistically different (P > 0.05) from the control. Whereas the absolute weights of the epididymis, seminal vesicle, and prostate were not affected, that of the testes was significantly increased. The epididymal sperm count, motility, morphology, and viscosity were not different from the control after 7 days of treatment. The male rat serum testosterone, progesterone, luteinizing hormone, and follicle-stimulating hormone significantly increased in the 25 and 50 mg/kg body weight groups, whereas the estradiol concentration decreased significantly at all the doses. The extract dose of 100 mg/kg body weight decreased the serum testosterone and progesterone levels in male rats. The prolactin concentration was not affected by all the doses. All the indices of reproduction, maternal, embryo/fetotoxic, teratogenic, and reproductive hormones in the female rats were not statistically different from that of their control except the resorption index, which increased at the dose of 100 mg/kg body weight of the extract. Histologic examination of the cross section of rat testes that received the extract at all the doses investigated revealed well-preserved seminiferous tubules with normal amount of stroma, normal population of spermatogenic and supporting cells, as well as normal spermatocytes within the lumen. The results revealed that the aqueous extract of Bulbine natalensis stem at doses of 25 and 50 mg/kg body weight enhanced the success rate of mating and fertility due to increased libido as well as the levels of reproductive hormones in male rats. The absence of alterations in the reproductive parameters of female rats at doses of 25 and 50 mg/kg body weight of Bulbine natalensis stem extract suggest that the extract is “safe” for use at these doses by females during the organogenic period of pregnancy, whereas the extract dose of 100 mg/kg body weight portends a negative effect on some reproductive functions of male and female rats.     

Teratogenic effects of a single oral administration of methylmercuric chloride in mice.

The teratogenic effects of methylmercuric chloride (MMC) given orally as a single dose to pregnant ICR mice on day 10 of gestation were examined. The doses tested were 25, 20, 15 and 10 mg/kg. Controls received distilled water orally. Each group consisted of 20 females. Fetuses were taken on day 18 of gestation for teratological study. The number of resorbed or dead embryos was moderately increased in the 25 mg/kg group. Fetuses from dams given 25, 20 and 15 mg/kg MMC weighed significantly less than those in the control group. Many fetuses with malformations were observed in the treated groups; cleft palate occurred in 100, 58.6 and 28.0% of fetuses from dams given 25, 20 and 15 mg/kg MMC, respectively (statistically significant). Hydronephrosis appeared in 23.8 and 18.5% of fetuses from dams given 25 and 20 mg/kg MMC, respectively (statistically significant). Skeletal variations, incomplete ossification of sternebrae, for example, were also observed in the treated groups. These results indicate that MMC is teratogenic so far as cleft palate is concerned and embryotoxic in ICR mice.     

Assessment of the mutagenic, antimutagenic and cytotoxic activities of ethanolic extract of araticum (Annona crassiflora Mart. 1841) by micronucleus test in mice.

A typical Brazilian plant, araticum (Annona crassiflora Mart.), is widely used in humans as therapeutic medicine to treat several diseases such as diarrhea, rheumatism and syphilis. It contains acetogenins which present cytotoxic, antitumogenic, and antiparasitic properties. In this study, mutagenic, antimutagenic and cytotoxic effects of araticum leaves ethanolic extract were evaluated by micronucleus test in mice. To evaluate the mutagenic activity, animals were treated with ethanolic extract of araticum (EEA) using 10, 20, 50, 100 and 160 mg.kg(-1). For all doses, micronucleated polychromatic erythrocytes (MNPCE) frequency was evaluated at 24, 48 and 72 hours after treatment. To evaluate the antimutagenic activity, animals were treated with 10, 20, 50 and 100 mg.kg(-1) of EEA and 4 mg.kg(-1) of MMC simultaneously. The frequency of MNPCE was evaluated 36 hours after exposure. Cytotoxicity was evaluated by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). In the mutagenicity assessment, all doses of EEA resulted in no significant increase of MNPCE (P > 0.05), compared to solvent- control group. Regarding administration time, no significant difference among three evaluation periods was observed (P > 0.05). Such results indicate that EEA did not exert mutagenic activity. Cytotoxicity was evident in doses of 50, 100 and 160 mg.kg(-1) at 24 and 48 hours after exposure. Concerning antimutagenicity, except the 10 mg.kg(-1) co-administered with 4 mg/kg of MMC, all doses reduced significantly the frequency of MNPCE compared to the positive control group (P < 0.05). These results, therefore, indicate an antimutagenic activity of the EEA. Cytotoxicity was significantly increased (P < 0.01) at 100 mg.kg(-1) EEA doses co-administered with 4 mg.kg(-1) of MMC.     

Effects of lead and hyperthermia on prenatal brain growth of guinea pigs

The effects of lead at blood levels of 100 micrograms/100ml or less on the brains of young animals have not been clearly defined, and little is known of its effects and interactions with other agents on prenatal brain development. This study examined the effects of subclinical doses of lead acetate given to pregnant guinea pigs on the development of the embryo brain. At 9 A.M. on day 20 or 21 of pregnancy, guinea pigs were given 6, 12.5, or 25 mg/kg body weight of 0.5% lead acetate in distilled water by intraperitoneal injection. Some of the animals at each dose rate were also exposed to hyperthermia at 11 A.M. on the day of injection and the following day. Another group was exposed to hyperthermia without lead treatment. A saline-treated control group was used for comparison. Mean levels of lead in blood 1 hour after dosing ranged between 65 and 128 micrograms/100 ml and at 24 and 72 hours between 65 and 96 micrograms/100 ml. Brain weights of newborn guinea pigs in the 12.5- and 25-mg lead acetate group were significantly reduced compared with control values. Body weights of all groups receiving lead were not significantly different from those of controls. There was no indication of interaction between hyperthermia and lead acetate in doses of 6 or 12.5 mg/kg. At 25 mg/kg plus hyperthermia, there appeared to be a strong synergistic response, with an incidence of 88% micrencephaly compared with 5% in the group given 25 mg/kg without hyperthermia and 46% in the hyperthermia without lead group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficiency of Coleus aromaticus extract in modifying cyclophosphamide and mitomycin-C induced clastogenicity in mouse bone marrow cells

The anticlastogenic potency of the ethanolic extract of a medicinal plant, C. aromaticus was investigated by taking bone marrow chromosomal aberration assay and micronucleus (MN) test as the test parameters. Swiss albino mice were fed orally with different doses (10,15, 25, 50 and 100 mg/kg body weight) of ethanolic extract for 7 days and on the 7th day, two doses each of anticancer drugs cyclophosphamide (CP; 25 and 50 mg/kg body weight) and mitomycin-C (MMC; 4 and 8 mg/kg body weight) were injected, ip, to different groups of animals. Bone marrow MN preparations were made at 24 and 48 hr time intervals. Coleus extract reduced CP and MMC induced MN and lower doses of the extract were found to be more effective than higher doses. The effective doses of extract in MN test were selected to study the anticlastogenic effects against CP (25 and 50 mg/kg body weight) and MMC (2 and 4 mg/kg body weight) induced chromosomal aberrations. The results indicate the protective effect of C. aromaticus against CP and MMC induced cytogenetic damage.     

Effects of Onosma armeniacum root extract on ethanol-induced oxidative stress in stomach tissue of rats

This study investigated the effects of Onosma armeniacum K. (Boraginaceae) root extract (AR-1) on ethanol-induced stomach ulcers, and on some oxidant and antioxidant parameters, in stomach tissue in rats. The results obtained showed that AR-1 significantly inhibited ethanol-induced ulcers at 25, 50, 100 and 200 mg/kg doses. We found that 50, 100 and 200 mg/kg doses of AR-1 inhibited ulcers more effectively than did ranitidine. AR-1 at doses of 25, 50, 100 and 200 mg/kg significantly prevented the decrease in total glutathione (tGSH) level which occurs in damaged stomach tissues of rats given ethanol (control group). Only a 100 mg/kg dose of AR-1 significantly increased the glutathione S-transferase (GST) level in stomach tissue compared to the control. All doses of AR-1 except the 25 mg/kg dose eliminated the decrease in the superoxide dismutase (SOD) level in the stomach tissue of rats given ethanol. While all doses of AR-1 decreased malondialdehyde (MDA) levels significantly; all doses AR-1 except 25 mg/kg decreased myeloperoxidase (MPO) levels significantly compared to the control. The effect of AR-1 on catalase (CAT) activity was insignificant at all doses. AR-1 significantly increased nitric oxide (NO) levels at 50, 100 and 200 mg/kg doses compared to the control. Our results indicate that the protection of some antioxidant mechanisms and the inhibition of some oxidant mechanisms have a role in AR-1's antiulcer effect mechanism.     

人参总皂苷和远志总苷配伍对小鼠抗抑郁作用

目的确定人参总皂苷（GTS）和远志总苷（PTG）抗抑郁配伍剂量比例,形成参远苷（SGY）制剂,为研制开发抗抑郁新药提供实验数据。方法采用析因设计方法,GTS和PTG均选取25、50、100 mg/kg三个剂量,按照完全随机的两因素3×3实验设计,得到参远苷的9个不同配比组。C57BL/6J小鼠（用于悬尾实验）和ICR小鼠（用于强迫游泳实验）随机分为对照组、阳性药组（10 mg/kg,帕罗西汀用于悬尾实验;阿米替林用于强迫游泳实验）及参远苷的9个不同配比组,共11组。灌胃给药7 d,观察各组对悬尾或强迫游泳实验小鼠不动时间的影响,并通过空场实验观察参远苷各配比对小鼠自主活动的影响。参远苷与单味GTS、PTG的抗抑郁作用比较实验中,C57BL/6J小鼠（用于悬尾实验）和ICR小鼠（用于强迫游泳实验）随机分为对照组、阳性药组（10 mg/kg,帕罗西汀用于悬尾实验;阿米替林用于强迫游泳实验）、参远苷低中高剂量组（37.5、75、150 mg/kg）、GTS和PTG各四个剂量组（均为18.75、37.5、75、150 mg/kg）,共13组。灌胃给药7 d,观察各组对悬尾或强迫游泳实验小鼠不动时间的影响。结果析因设计结果表明,GTS和PTG之间无交互效应。参远苷配比组75 mg/kg（GTS∶PTG为50∶25）及150mg.kg-1（GTS∶PTG为100∶50）显著并稳定缩短悬尾或强迫游泳不动时间（P〈0.05）,得出GTS和PTG的剂量配伍比例为2：1。空场实验结果显示,参远苷各配比对小鼠运动总路程无影响。参远苷与单味GTS、PTG抗抑郁作用比较实验结果显示,GTS 75、150 mg/kg缩短悬尾实验小鼠不动时间（P〈0.01,P〈0.05）,对强迫游泳实验小鼠不动时间无影响。PTG 18.75、37.5 mg/kg缩短强迫游泳实验小鼠不动时间（P〈0.01,P〈0.05）,对悬尾实验小鼠不动时间无影响。参远苷75、150 mg/kg缩短悬尾实验小鼠不动时间（P〈0.05）。同时,参远苷37.5、75 mg/kg缩短强迫游泳实验小鼠不动时间（P〈0.01,P〈0.05）。结论 GTS和PTG以2：1的比例形成的参远苷（SYG）制剂,质量容易控制,作用机制多样,符合抑郁症复杂多样的发病机制,优于单味GTS和PTG,进一步研究之后,有可能成为新型的抗抑郁药物。